Repeated porphyrin lipoprotein-based photodynamic therapy controls distant disease in mouse mesothelioma via the abscopal effect
Abstract
While photodynamic therapy (PDT) can induce acute inflammation in the irradiated tumor site, a sustained systemic, adaptive immune response is desirable, as it may control the growth of nonirradiated distant disease. Previously, we developed porphyrin lipoprotein (PLP), a ∼20 nm nanoparticle photosensitizer, and observed that it not only efficiently eradicated irradiated primary VX2 buccal carcinomas in rabbits, but also induced regression of nonirradiated metastases in a draining lymph node. We hypothesized that PLP-mediated PDT can induce an abscopal effect and we sought to investigate the immune mechanism underlying such a response in a highly aggressive, dual subcutaneous AE17-OVA+ mesothelioma model in C57BL/6 mice. Four cycles of PLP-mediated PDT was sufficient to delay the growth of a distal, nonirradiated tumor four-fold relative to controls. Serum cytokine analysis revealed high interleukin-6 levels, showing a 30-fold increase relative to phosphate-buffered solution (PBS) treated mice. Flow cytometry revealed an increase in CD4+ T cells and effector memory CD8+ T cells in non-irradiated tumors. Notably, PDT in combination with PD-1 antibody therapy prolonged survival compared to monotherapy and PBS. PLP-mediated PDT shows promise in generating a systemic immune response that can complement other treatments, improving prognoses for patients with metastatic cancers.
Journal
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- Nanophotonics
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Nanophotonics 10 (12), 3279-3294, 2021-08-02
Walter de Gruyter GmbH
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Details 詳細情報について
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- CRID
- 1050570543450856448
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- NII Article ID
- 120007126834
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- ISSN
- 21928614
- 21928606
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- HANDLE
- 2115/82445
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- Text Lang
- en
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- Article Type
- journal article
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- Data Source
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- IRDB
- Crossref
- CiNii Articles
- KAKEN